Objective: To investigate the effects of circulating exosomes derived from oral cancer patients on the proliferation, migration and invasion of tongue cancer CAL27 cells. Methods: Circulating exosomes were isolated from the peripheral blood of 20 oral cancer patients using gradient centrifugation. The characteristics of the exosome was studied by transmission electron microscope (TEM) and Western blot. After treatment with circulating exosomes, CAL27 cell proliferation was evaluated with MTT assay, migration was observed by cell wound scratch assay and the invasion of CAL27 cells was tested by Transwell assay. CAL27 cell bearing nude mice were used to estimate the effect of circulating exosome on CAL27 cell proliferation and metastasis in vivo. Results: The proliferation, migration and invasion of CAL27 cells were enhanced by circulating exosomes from oral cancer patients. In vivo study showed that the tumorigenesis and metastasis of CAL27 cells were enhanced by circulating exosomes. Conclusion: Circulating exosomes from oral cancer patients can promote the proliferation, migration, invasion and metastasis of CAL27 cells.

Objective To investigate the influence of mismatch repair status on clinicopathological characteristics and prognosis in patients with colon cancer.Methods Patients who underwent radical excision for colon cancer between Nov 2012 and Mar 2016 at Peking University People's Hospital were enrolled.Clinicopathological data and prognosis were collected.Multivariate analysis were used to identify independent characteristics of MMR-deficient colon cancer.The influence of MMR-deficient on prognosis of colon cancer were analyzed through Kaplan-Meier curve.Results The overall rate of MMR-deficient in colon cancer was 17.1％ (51/299).Multivariate logistic regression analysis showed that low differentiation (OR =3.555,95％ CI:1.685-7.640,P ＜ 0.001),right-sided colon cancer (OR =5.645,95％ CI:2.483-14.715,P ＜ 0.001) and UICC Stage Ⅰ-Ⅱ (OR =4.099,95％ CI:1.863-9.840,P ＜0.001) were associated with MMR-deficient colon cancer.Conclusion Low differentiation,right-sided colon cancer and UICC Stage Ⅰ-Ⅱ were more common in MMR-deficient colon cancer.

Objective To investigate the correlation between quantitative parameters derived from iodine overlay images and the monochromatic images of dual‐energy CT and the differentiation degree of laryngeal and hypopharyngeal squamous cell carcinoma(LHSCC). Methods Retrospective analysis of clinical and imaging data of eighty patients with different differentiation degree of LHSCC who underwent dual‐energy CT enhanced scan in the arterial and venous phase from March 2016 to January 2017 (20, 42 and 18 patients with well, moderately and poorly differentiation, respectively) was performed.Among them, twenty‐eight cases were stage T1, twenty‐four cases were stage T2, twenty cases were stage T3 and eight cases were stage T4. All patients were not treated with radiotherapy and chemotherapy before operation. Iodine overlay images and the monochromatic images of arterial and venous phases were acquired from Syngo MultiModality Workplace dual‐energy post‐processing software of Siemens, respectively. The mean iodine concentration (IC), standardized iodine concentration (SIC), and the slope of spectral curve(λ) of different differentiation degrees of LHSCC were calculated and compared. The correlation between quantitative parameters of LHSCC and its differentiation degree was performed by Spearman rank sum test. One‐way analysis of variance was used to compare the quantitative parameters of different differentiation degree of LHSCC. Receiver operating characteristic (ROC) curve was used for analyzing diagnostic efficiency. Results The IC, SIC, and λ in the arterial phase, and IC in the venous phase correlated positively with differentiation degree in LHSCC (r=0.258, 0.350, 0.262 and 0.275, respectively; P<0.05) in this group. The IC, SIC, and λ of poorly differentiated LHSCC in the arterial phase [(3.13 ± 0.54) mg/ml, (0.38±0.10), (5.40±0.92)] were higher than those of well differentiated LHSCC [(2.38±1.02) mg/ml, (0.25± 0.09) and (4.19 ± 1.18); t=2.73, 3.36 and 2.75 respectively; P<0.05] and moderately differentiated LHSCC [(2.56±0.85) mg/ml, (0.28±0.16) and (4.56±1.41); t=2.38, 3.06 and 2.21, P<0.05]. IC of poorly differentiated LHSCC in the venous phase [(2.59 ± 0.62) mg/ml] was significantly higher than that of well differentiated LHSCC [(1.96±0.56) mg/ml,t=2.45,P<0.05] and moderately differentiated [(2.02±0.93) mg/ml,t=2.56,P<0.05] LHSCC. There was no significant difference in the SIC and λ between different differentiation degrees of LHSCC (P>0.05) in the venous phase. The standardized iodine concentration in the arterial phase was the best in distinguishing poorly and moderately differentiated LHSCC, and poorly and well differentiated LHSCC with the area under the receiver operating curve 0.77 and 0.81, respectively, the sensitivity 88.2% and 70.0%, respectively, and the specificity 69.0% and 70.0%, respectively. Conclusions Quantitative parameters derived from dual‐energy CT might be useful in the evaluation of different differentiated degrees of LHSCC. In addition, the standardized iodine concentration of LHSCC in the arterial phase was the best in the estimation of different differentiated degrees of LHSCC.

Angiotensin (Ang)-(1-7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1-7) in the hypothalamic paraventricular nucleus (PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines (PICs) and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt (8% NaCl) or a normal salt diet (0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1-7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma norepinephrine (NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 expression and superoxide production in the PVN. Microinjection of A-779 (3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1-7) in the PVN, through modulation of PICs and oxidative stress.
Angiotensin I ; antagonists & inhibitors ; metabolism ; Animals ; Antioxidants ; pharmacology ; Blood Pressure ; drug effects ; Hypertension ; chemically induced ; drug therapy ; Male ; Oxidative Stress ; drug effects ; Paraventricular Hypothalamic Nucleus ; drug effects ; Peptide Fragments ; antagonists & inhibitors ; metabolism ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Sodium Chloride, Dietary ; pharmacology

Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha (PPAR-α), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-α and PPAR-γ was assessed in the nodose ganglion (NG) and the nucleus of the solitary tract (NTS). Hypertension induced by drinking high fructose (HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-α and PPAR-γ were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-α, the mitochondrial uncoupling protein 2 (UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats. These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.
Afferent Pathways ; drug effects ; Animals ; Antihypertensive Agents ; pharmacology ; Baroreflex ; drug effects ; Blood Pressure ; drug effects ; Fenofibrate ; pharmacology ; Male ; Oxidative Stress ; drug effects ; PPAR gamma ; drug effects ; metabolism ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transcriptional Activation ; drug effects ; Uncoupling Protein 2 ; drug effects ; metabolism ; Up-Regulation

The solubility of nebivolol hydrochloride was determined in acidic aqueous media in the absence and presence of different concentration of NaCl, NaBr, or NaI at 37 ℃ in order to facilitate proper selection of dissolution media that have adequate discriminating power for enhancing the likelihood of a generic drug product to successfully pass in-vivo bioequivalence test. In the range of pH 5.0 to pH 1.0, the solubility of nebivolol hydrochloride decreased with the decrease in the pH of aqueous solution, and the solubility of nebivolol hydrochloride further decreased with the increase in the concentration of added sodium chloride. The solubility decrease of a few weakly basic drug molecules in acidic media and in higher concentration of added chloride was published previously by other researchers, and the observed decrease in the solubility in the presence of higher chloride concentration was interpreted in terms of common-ion effect. However, the results in this paper showed that the solubility of nebivolol hydrochloride also decreased when sodium chloride was replaced with sodium bromide or iodide. The approach described in this paper (i.e. substituting sodium chloride with sodium bromide or iodide) provides an effective method to verify whether common-ion effect is the true (or at least the sole) driving force behind the observed decrease in the solubility of nebivolol hydrochloride in the presence of sodium chloride. The solubility decrease reported in this paper can be interpreted in terms of salting-out effect of sodium chloride, bromide, and iodide. For hydrochloride salt of a weakly basic drug molecule like nebivolol hydrochloride, its solubility in an acidic dissolution medium can be purposely decreased to the lower end of sink condition by adding sodium chloride to make the resulting medium more discriminating. As shown in this paper, a medium at pH 1.2 with added sodium chloride is discriminating and this medium is shown to be bio-relevant to the in-vivo data collected under fasting condition (in-vivo study protocol was approved by Institutional Review Board).

Objective To investigate whether elevated baseline levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) are associated with an increased risk of breast cancer in Kailuan female cohort. Methods Females from Kailuan cohort (2006-2007) were included in this study. Information on check-up, hsCRP and NE were collected at baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) of association between baseline hsCRP and NE values and breast cancer risk. Results By December 31, 2015, a total of 18 866 participants were enrolled in this study. During the follow-up, 183 new cases of breast cancer were observed. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of breast cancer were 829/105, 1 211/105 and 1 495/105 in these 3 groups, respectively ( 2=12.08， P=0.002). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significantly increased risk of breast cancer (HR=1.71,95%CI: 1.18-2.47, P=0.005), howerver, we didn’t find the statistically significant association between NE level (<3.70×109/Lvs. ≥3.70×109/L) and the risk of brease cancer (P>0.05). Conclusions Elevated levels of hsCRP at baseline might increase the risk of breast cancer in females.

Objective To explore the feasibility and safety of endovascular directional atherectomy angioplasty for the treatment of severe vertebral artery stenosis.Methods Directional atherectomy combined with use of drug-coating balloon (DCB) was employed to treat one patient with severe stenosis of vertebral artery in November 2017 at authors' hospital.Protective umbrella filter was placed at the distal site of V1 segment during the procedure course.Results The operation was successfully accomplished.No postoperative complications occurred.After the operation,the clinical symptom of dizziness disappeared and the patient was well recovered.Conclusion For the treatment of severe vertebral artery stenosis,directional atherectomy combined with use of DCB is safe and feasible.

Objective To investigate the relationship between angiotensin converting enzyme(ACE) gene polymorphism and carotid plaque composition,vessel wall morphology,and clinical symptoms based on vessel wall magnetic resonance imaging. Methods Totally 75 hypertensive patients(75 internal carotid artery plaques) with maximum plaque thickness≥1.5 mm,according to the ACE insertion(I) or deletion(D) gene polymorphism,were divided into ACE 2 genotype group(n=37) and ACE ID/DD genotype group(n=38). The influences of plaque composition,vessel wall morphology,clinical symptoms,and use of ACE inhibitor or angiotensin receptor blocker(ACEI/ARB) on vessel wall morphology were analyzed. Results Compared with ACE 2 genotype group,the ACE ID/DD genotype group had significantly higher incidence of ischemic stroke(Χ=3.921,P=0.048). The plaque composition and vessel wall morphology showed no significant difference between these two groups. Inside ACE ID/DD genotype group,the carotid remodeling index was significantly lower in users of ACEI/ARB than non-users of ACEI/ARB(1.85±0.60 vs. 2.48±0.40;t=3.854,P=0.001).Conclusion In primary hypertension,ACE ID/DD genotype may be associated with carotid atherosclerotic plaque.

BackgroundAntimicrobial de-escalation refers to starting the antimicrobial treatment with broad-spectrum antibiotics, followed by narrowing the drug spectrum according to culture results. The present study evaluated the effect of de-escalation on ventilator-associated pneumonia (VAP) in trauma patients.

MethodsThis retrospective study was conducted on trauma patients with VAP, who received de-escalation therapy (de-escalation group) or non-de-escalation therapy (non-de-escalation group). Propensity score matching method was used to balance the baseline characteristics between both groups. The 28-day mortality, length of hospitalization and Intensive Care Unit stay, and expense of antibiotics and hospitalization between both groups were compared. Multivariable analysis explored the factors that influenced the 28-day mortality and implementation of de-escalation.

ResultsAmong the 156 patients, 62 patients received de-escalation therapy and 94 patients received non-de-escalation therapy. No significant difference was observed in 28-day mortality between both groups (28.6% vs. 23.8%, P = 0.620). The duration of antibiotics treatment in the de-escalation group was shorter than that in the non-de-escalation group (11 [8-13] vs. 14 [8-19] days, P = 0.045). The expenses of antibiotics and hospitalization in de-escalation group were significantly lower than that in the non-de-escalation group (6430 ± 2730 vs. 7618 ± 2568 RMB Yuan, P = 0.043 and 19,173 ± 16,861 vs. 24,184 ± 12,039 RMB Yuan, P = 0.024, respectively). Multivariate analysis showed that high Acute Physiology and Chronic Health Evaluation II (APACHE II) score, high injury severity score, multi-drug resistant (MDR) infection, and inappropriate initial antibiotics were associated with patients' 28-day mortality, while high APACHE II score, MDR infection and inappropriate initial antibiotics were independent factors that prevented the implementation of de-escalation.

ConclusionsDe-escalation strategy in the treatment of trauma patients with VAP could reduce the duration of antibiotics treatments and expense of hospitalization, without increasing the 28-day mortality and MDR infection.

APACHE ; Anti-Bacterial Agents ; therapeutic use ; Female ; Humans ; Intensive Care Units ; Male ; Pneumonia, Ventilator-Associated ; drug therapy ; pathology ; Propensity Score ; Retrospective Studies